Olivier Keunen

Olivier Keunen
LIH Luxembourg Institute of Health | CRP Santé · Department of Cancer Research

PhD
Principal Investigator, Translational Radiomics Group, Luxembourg Institute of Health

About

74
Publications
8,465
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1,565
Citations

Publications

Publications (74)
Preprint
An orthotopically xenografted mouse GL26 glioma model (Ccr2 RFP/wt -Cx3cr1 GFP/wt ) was used to evaluate the effect of transient, focal opening of the Blood Brain Barrier (BBB) on the composition of tumor-associated macrophages and microglia (TAMs). Opening of the BBB was induced by Magnetic Resonance Imaging (MRI)-guided focused ultrasound (MRgFUS...
Poster
BACKGROUND Extensive tumor cell invasion within the brain represents a major problem for effective treatment of glioblastomas (GBMs). The invasive processes can be divided into three types: Collective cell invasion, perivascular infiltration, and single-cell invasion into the brain parenchyma. GBM cells can form synapses with neural cells pointing...
Article
Full-text available
Brain metastasis (BM) is a major cause of cancer patient morbidity. Clinical magnetic resonance imaging (MRI) and positron emission tomography (PET) represent important resources to assess tumor progression and treatment responses.In preclinical research, anatomical MRI and to some extent functional MRI have frequently been used to assess tumor pro...
Presentation
BACKGROUND Extensive tumor cell invasion within the brain represents a major problem for effective treatment of glioblastomas (GBMs). The invasive processes can be divided into three types: Collective cell invasion, perivascular infiltration and single-cell invasion into the brain parenchyma. It has recently been shown that GBM cells have the abili...
Article
Full-text available
Tumor organoids and patient-derived orthotopic xenografts (PDOXs) are some of the most valuable pre-clinical tools in cancer research. In this protocol, we describe efficient derivation of organoids and PDOX models from glioma patient tumors. We provide detailed steps for organoid culture, intracranial implantation, and detection of tumors in the b...
Article
Surgery can be highly effective for treating certain cases of drug resistant epilepsy. The current study tested a novel, non-invasive, surgical strategy for treating seizures in a rat model of temporal lobe epilepsy. The surgical approach uses magnetic resonance-guided, low-intensity focused ultrasound (MRgFUS) in combination with intravenous micro...
Article
Full-text available
Patient-based cancer models are essential tools for studying tumor biology and for the assessment of drug responses in a translational context. We report the establishment a large cohort of unique organoids and patient-derived orthotopic xenografts (PDOX) of various glioma subtypes, including gliomas with mutations in IDH1, and paired longitudinal...
Preprint
Full-text available
Patient-derived cancer models are essential tools for studying tumor biology and preclinical interventions. Here, we show that glioma patient-derived orthotopic xenografts (PDOXs) enable long-term propagation of patient tumors and represent clinically relevant patient avatars. We created a large collection of PDOXs from primary and recurrent glioma...
Article
Patients with melanoma have a high risk of developing brain metastasis, which is associated with a dismal prognosis. During early stages of metastasis development, the blood-brain barrier (BBB) is likely intact, which inhibits sufficient drug delivery into the metastatic lesions. We investigated the ability of the peptide, K16ApoE, to permeabilize...
Article
Full-text available
BACKGROUND: Melanoma patients have a high risk of developing brain metastases, which is associated with a poor prognosis. The blood-brain barrier (BBB) inhibits sufficient drug delivery into metastatic lesions. We investigated the ability of a synthetic peptide (K16ApoE) to permeabilize the BBB for more effective drug treatment. METHODS: DCE-MRI wa...
Article
Purpose: The Tofts and the extended Tofts models are the pharmacokinetic models commonly used in dynamic contrast-enhanced MRI (DCE-MRI) perfusion analysis, although they do not provide two important biological markers, namely, the plasma flow and the permeability-surface area product. Estimates of such markers are possible using advanced pharmaco...
Chapter
This paper introduces new variational formulation for reconstruction from subsampled dynamic contrast-enhanced DCE-MRI data, that combines a data-driven approach using estimated temporal basis and total variation regularization (PCA TV). We also experimentally compares the performance of such model with two other state-of-the-art formulations. One...
Article
Full-text available
Individuals with brain metastasis usually await a poor prognosis. Even with the ongoing development of novel targeted therapies, a major impediment in the treatment of brain metastasis is delivering of drugs across the blood-brain/tumor barrier. Different strategies to accomplish temporary opening of the heterogenous blood-brain barrier have been d...
Article
Full-text available
Glioblastoma (GBM) is a typically lethal type of brain tumor with a median survival of 15 months postdiagnosis. This negative prognosis prompted the exploration of alternative treatment options. In particular, the reliance of GBM on angiogenesis triggered the development of anti-VEGF (vascular endothelial growth factor) blocking antibodies such as...
Article
Patients with brain metastases usually have a poor prognosis. Regardless of the constant progress in novel drug establishments, a crucial obstacle is the delivery of drugs across the blood brain barrier (BBB) and into the metastatic neoplasms. Different study designs to achieve temporary BBB opening have previously been studied. Here, we describe a...
Article
Heterozygous mutations in NADP-dependent isocitrate dehydrogenases (IDH) define the large majority of diffuse gliomas and are associated with hypermethylation of DNA and chromatin. The metabolic dysregulations imposed by these mutations, whether dependent or not on the oncometabolite D-2-hydroxyglutarate (D2HG), are less well understood. Here, we a...
Article
Introduction: Patients with brain metastases await a dismal prognosis. Regardless of the continuous progress in drug development, a major problem is the delivery of drugs across the blood brain barrier (BBB) and into the metastatic neoplasms. The BBB excludes almost all compounds, in particular highly charged, hydrophilic or large compounds, and mo...
Article
Full-text available
Neo-angiogenesis represents an important factor for the delivery of oxygen and nutrients to a growing tumour, and is considered to be one of the main pathodiagnostic features of glioblastomas (GBM). Anti-angiogenic therapy by vascular endothelial growth factor (VEGF) blocking agents has been shown to lead to morphological vascular normalisation res...
Article
Full-text available
Individuals with metastatic disease within the brain usually await a poor prognosis. Regardless of the ongoing development of novel drugs, a significant challenge is the delivery of drugs across the blood brain barrier (BBB) and into the metastatic neoplasms. The BBB excludes almost all therapeutic compounds, as highly charged, hydrophilic or large...
Article
Full-text available
Background The aggressive potential of glioblastoma (GBM) is partially due to its highly invasive behaviour. Since invasive cells cannot be easily removed by surgery or irradiation, this tumour always recurs and is eventually lethal. Therefore it is crucial to elucidate the process of invasion in GBM to identify the key genes underlying the invasiv...
Article
Background: The efficiency of traditional anthropometric measurements such as body mass index (BMI) or waist circumference (Waist C) used to replace biomedical imaging for assessing visceral adipose tissue (VAT) is still highly controversial in youth. Hypothesis and objectives: We evaluated the most accurate model predicting VAT in overweight/ob...
Article
Background Amplification of the epidermal growth factor receptor (EGFR) and its mutant EGFRvIII are among the most common genetic alterations in glioblastoma (GBM), the most frequent and most aggressive primary brain tumor. Methods In the present work, we analyzed the clonal evolution of these major EGFR aberrations in a small cohort of GBM patien...
Article
Full-text available
L-Glutamine (Gln) functions physiologically to balance the carbon and nitrogen requirements of tissues. It has been proposed that in cancer cells undergoing aerobic glycolysis, accelerated anabolism is sustained by Gln-derived carbons, which replenish the tricarboxylic acid (TCA) cycle (anaplerosis). However, it is shown here that in glioblastoma (...
Article
Full-text available
The histopathological and molecular heterogeneity of glioblastomas represents a major obstacle for effective therapies. Glioblastomas do not develop autonomously, but evolve in a unique environment that adapts to the growing tumour mass and contributes to the malignancy of these neoplasms. Here, we show that patient-derived glioblastoma xenografts...
Article
Full-text available
OBJECTIVE: Glioblastomas (GBM) are highly angiogenic tumors and were initially perceived as good candidates for anti -angiogenic therapy. Bevacuzimab, a monoclonal anti-VEGF antibody, was approved by the FDA in 2009 as monotherapy for recurrent GBM, but recent phase III clinical studies revealed no overall survival benefit, yet with a small improve...
Article
Full-text available
Epigenetic modifications play a major role in the development of multiple myeloma. We have previously reported that the PPARγ agonist pioglitazone (PIO) enhances, in-vitro, the cytotoxic effect of the Histone deacetylase inhibitor (HDACi), valproic acid (VPA), on multiple myeloma cells. Here, we described the development of a new multiple myeloma m...
Article
Childhood obesity is associated with early cardiometabolic risk (CMR), increased risk of adulthood obesity, and worse health outcomes. Leg fat mass (LFM) is protective beyond total fat mass (TFM) in adults. However, the limited evidence in children remains controversial. We investigated the relationship between LFM and CMR factors in youth. A total...
Conference Paper
Full-text available
EGFR gene amplification is observed in upwards of 40% of glioblastoma (GBM) biopsies, and genetic aberration to EGFR at large has been described to occur in excess of 50%. Our lab has developed a clinically relevant in vivo xenograft model derived from patient biopsies in which we are able to accurately study EGFR signaling in human GBM. We previou...
Article
Full-text available
Anti-angiogenic therapy in glioblastoma (GBM) has unfortunately not led to the anticipated improvement in patient prognosis. We here describe how human GBM adapts to bevacizumab treatment at the metabolic level. By performing 13C6-glucose metabolic flux analysis, we show for the first time that the tumors undergo metabolic re-programming toward ana...
Article
Full-text available
The vast majority of malignant gliomas relapse after surgery and standard radio-chemotherapy. Novel molecular and cellular therapies are thus being developed, targeting specific aspects of tumor growth. While histopathology remains the gold standard for tumor classification, neuroimaging has over the years taken a central role in the diagnosis and...
Conference Paper
Full-text available
The epidermal growth factor receptor (EGFR) is a well-known mediator of invasion, proliferation and survival of tumor cells. Amplification and associated overexpression of wild-type (wt) EGFR is the most common genetic alteration in primary glioblastoma (GBM), with a frequency of about 40-50%. Of the GBMs that have an amplification of EGFR, 50-60%...
Article
Full-text available
We have in two different xenograft model systems of human glioblastoma (GBM) that reflect the genotype and phenotype of human GBMs, assessed using 13C6-glucose metabolomic flux analysis, how the tumors adapt to anti-vascular therapy (bevacizumab treatment). A detailed LC-MS analyses of 13C-labeled metabolites show that the tumors adapt to therapy b...
Article
Full-text available
Treatment of primary and recurrent glioblastoma with anti-angiogenic therapies, either alone or in combination with chemotherapy, fails to extend overall survival, despite the often reported improvements in progression free survival and patient health condition. To improve the efficacy of these therapies, a better understanding of the mechanisms of...
Article
Full-text available
Glioblastomas (GBMs) are highly vascular tumors. Therefore, anti-vascular therapy has been regarded as a promising treatment strategy. Yet, recent results from two double-blind, placebo-controlled phase III trials, (RTOG 0825), and (AVAglio), for first-line treatment of GBM patients did not show any improvement of overall survival. In order to prov...
Article
Full-text available
Recent results from 2 double-blind, placebo-controlled phase III trials (RTOG 0825) and (AVAglio) for first-line treatment of glioblastoma patients with the VEGF antibody bevacizumab, showed similar results, related to overall and progression-free survival. The RTOG 0825 trial indicated, opposed to the AVAglio trial, that patients treated with beva...
Article
Full-text available
Background Deregulated growth factor signaling is a major driving force in the initiation and progression of glioblastoma. The tumor suppressor and stem cell marker Lrig1 is a negative regulator of the epidermal growth factor receptor (EGFR) family. Here, we addressed the therapeutic potential of the soluble form of Lrig1 (sLrig1) in glioblastoma t...
Article
Full-text available
Angiogenesis is regarded as a hallmark of cancer progression and it has been postulated that solid tumor growth depends on angiogenesis. At present, however, it is clear that tumor cell invasion can occur without angiogenesis, a phenomenon that is particularly evident by the infiltrative growth of malignant brain tumors, such as glioblastomas (GBMs...
Conference Paper
Glioblastoma (GBM) is the most aggressive form of primary brain tumors with a median survival of 15 months. Although angiogenesis is one of the main features of GBMs, non-angiogenic tumor infiltration into brain parenchyma still is the major challenge for therapy. Tumor cells can migrate very far from the main tumor mass and the invasive pattern of...
Article
Full-text available
Bevacizumab, an antibody against vascular endothelial growth factor (VEGF), is a promising, yet controversial, drug in human glioblastoma treatment (GBM). Its effects on tumor burden, recurrence, and vascular physiology are unclear. We therefore determined the tumor response to bevacizumab at the phenotypic, physiological, and molecular level in a...
Conference Paper
Full-text available
To get more information about tissue perfusion from T 1 -weighted dynamic contrast enhanced magnetic resonance imaging, more complex models than the commonly accepted Kety model have to be used. However using adiabatic approximation to the tissue homogeneity model (ATH) brings serious convergence problems, caused mainly by discontinuities in the cr...

Projects

Project (1)
Project
Setting up of a national platform from preclinical in vivo imaging in Luxembourg